Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair.

The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in non-homologous end-joining (NHEJ) repair. We investigated the mechanism of NU7441, a highly selective DNA-PK inhibitor, in NHEJ-competent mouse embryonic fibroblast (MEF) cells and NHEJ-deficient cells and explored the feasibility of its application in radiosensitizing nasopharyngeal carcinoma (NPC) cells. We generated wild-type and DNA-PKcs-/- MEF cells.

Empowering Intensity Modulated Proton Therapy Through Physics and Technology: An Overview.

Considering the clinical potential of protons attributable to their physical characteristics, interest in proton therapy has increased greatly in this century, as has the number of proton therapy installations. Until recently, passively scattered proton therapy was used almost entirely. Notably, the overall clinical results to date have not shown a convincing benefit of protons over photons.

Inhibiting DNA-PKcs in a non-homologous end-joining pathway in response to DNA double-strand breaks.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a distinct factor in the non-homologous end-joining (NHEJ) pathway involved in DNA double-strand break (DSB) repair. We examined the crosstalk between key proteins in the DSB NHEJ repair pathway and cell cycle regulation and found that mouse embryonic fibroblast (MEF) cells deficient in DNA-PKcs or Ku70 were more vulnerable to ionizing radiation (IR) compared with wild-type cells and that DSB repair was delayed. γH2AX was associated with phospho-Ataxia-telangiectasia mutated kinase (Ser1987) and phospho-checkpoint effector kinase 1 (Ser345) foci for the arrest of cell cycle through the G2/M phase.

Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head and neck cancer.

Purpose: Hypoxia is one of the main causes of the failure to achieve local control using radiotherapy. This is due to the increased radioresistance of hypoxic cells. (18)F-fluoromisonidazole ((18)F-FMISO) positron emission tomography (PET) is a noninvasive imaging technique that can assist in the identification of intratumor regions of hypoxia.

Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study.

Purpose: Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV(h)) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV(h) increases the tumor control probability.

Adenovirus-mediated expression of a dominant negative Ku70 fragment radiosensitizes human tumor cells under aerobic and hypoxic conditions.

Ku70 is one component of a protein complex, the Ku70/Ku80 heterodimer, which binds to DNA double-strand breaks and activates DNA-dependent protein kinase (DNA-PK), leading to DNA damage repair. Our previous work has confirmed that Ku70 is important for DNA damage repair in that Ku70 deficiency compromises the ability of cells to repair DNA double-strand breaks, increases the radiosensitivity of cells, and enhances radiation-induced apoptosis. Because of the radioresistance of some human cancers, particularly glioblastoma, we examined the use of a radio-gene therapy paradigm to sensitize cells to ionizing radiation.

Integrating respiratory gating into a megavoltage cone-beam CT system.

We have previously described a low-dose megavoltage cone beam computed tomography (MV CBCT) system capable of producing projection image using one beam pulse. In this study, we report on its integration with respiratory gating for gated radiotherapy. The respiratory gating system tracks a reflective marker on the patient's abdomen midway between the xiphoid and umbilicus, and disables radiation delivery when the marker position is outside predefined thresholds.

Intensity-modulated radiotherapy as the boost or salvage treatment of nasopharyngeal carcinoma: the appropriate parameters in the inverse planning and the effect of patient's anatomic factors on the planning results.

The current study demonstrates that the large increase in normal tissue penalty often degrades target dose uniformity without a concomitant large improvement in normal tissue dose, especially in anatomically unfavorable patients. The excessively large normal tissue penalties do not improve treatment plans for patients having unfavorable geometry.

Reduction of organ motion in lung tumors with respiratory gating.

We evaluated the ability of a commercial respiratory gating system to assure the reproducibility of internal anatomy in respiration synchronized CT (RS-CT) scans. This passive system uses an infrared sensitive camera to track the motion of reflective markers mounted on the abdomen. Eighteen patients, nine with lung tumors and nine with liver tumors, were selected for evaluation of the Varian Real-Time Position Monitor respiratory gating system.

Changes in FDG Tumor Uptake during and after Fractionated Radiation Therapy in a Rodent Tumor Xenograft.

OBJECTIVE: The uptake of FDG was measured before, during, and after fractionated radiation in order to evaluate the potential of FDG-PET imaging as an indicator of tumor response.METHODS: The study was performed with nude rats bearing the human neuroblastoma BE(2)C tumor xenografts. Tumors were irradiated with 10 fractions of 2 Gy using a 320 kV(p) X-ray unit.

Evaluation of rapid dose map acquisition of a scanning liquid-filled ionization chamber electronic portal imaging device.

Purpose: We evaluated the performance of a new dosimetry module in the LC250 scanning liquid-filled ionization chamber (SLIC) electronic portal imaging device (EPID) for intensity-modulated radiotherapy (IMRT) verification. This module permits one to convert EPID readings to two-dimensional (2D) maps of IMRT dose rate in real time, and to integrate them over time to produce a profile of accumulated dose for treatment verification.

Methods And Materials: The EPID was calibrated using an iterative procedure, from which a lookup table for dose integration was generated and transferred to the image-acquisition hardware.

Development of a semi-automatic alignment tool for accelerated localization of the prostate.

Purpose: Delivering high dose to prostate with external beam radiation has been shown to improve local tumor control. However, it has to be carefully performed to avoid partial target miss and delivering excessive dose to surrounding normal tissues. One way to achieve safe dose escalation is to precisely localize prostate immediately before daily treatment.

Optimization of conformal thoracic radiotherapy using cone-beam CT imaging for treatment verification.

Purpose: Megavoltage cone-beam computed tomography (MVCBCT) has been proposed for treatment verification in conformal radiotherapy. However, the doses required for such imaging may compromise the quality of the delivered dose distribution. The present paper explores the effect of cone-beam imaging on dose homogeneity and critical organ dose and the use of our new tool, adapted intensity-modulated radiation therapy (AIMRT).

Evaluation of concave dose distributions created using an inverse planning system.

Purpose: To evaluate and develop optimum inverse treatment planning strategies for the treatment of concave targets adjacent to normal tissue structures.

Methods And Materials: Optimized dose distributions were designed using an idealized geometry consisting of a cylindrical phantom with a concave kidney-shaped target (PTV) and cylindrical normal tissues (NT) placed 5-13 mm from the target. Targets with radii of curvature from 1 to 2.

Effect of respiratory gating on quantifying PET images of lung cancer.

Unlabelled: We have developed a new technique to gate lung 18F-FDG PET images in synchronization with the respiratory motion to reduce smearing due to breathing and improve quantitation of 18F-FDG uptake in lung lesions.

Methods: A camera-based respiratory gating system, the real-time position management (RPM), is used to monitor the respiratory cycle. The RPM provides a trigger to the PET scanner to initiate the gating cycle.

Intensity-modulated radiotherapy versus conventional three-dimensional conformal radiotherapy for boost or salvage treatment of nasopharyngeal carcinoma.

Purpose: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC.

Methods And Materials: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5-7 radiation fields were created for each patient using an inverse treatment planning system.